Minor physical anomalies in patients with schizophrenia and their parents: prevalence and pattern of craniofacial abnormalities

The frequency of minor physical anomalies (MPAs) in patients with schizophrenia suggests an early disturbance in the development of the neuroectoderm. To improve the phenotypic delimitation of this disorder, we used a comprehensive scale of MPAs (41 items) in patients with schizophrenia and their first-degree relatives. This scale, adapted from a revised version of the Waldrop Scale (Ismail et al. Minor physical anomalies in schizophrenic patients and their siblings, American Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing facial and limbs asymmetry. The interrater reliability between two examiners was good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45; mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of several items to predict group status, including facial asymmetry, cleft palate, hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry in patients with schizophrenia and their first-degree relatives provides new insights into the underlying dysembryogenic processes. This revised scale thus appears to be a useful complementary tool in pathophysiological studies aiming at the identification of developmental factors in schizophrenia.     

French validation of a Minor Morphologic Anomalies Scale in schizophrenic patients and their parents]

Minor Physical Anomalies represent valuable indices of disturbance in early neurodevelopment. They are frequently observed in individuals with various brain disorders, including mental retardation, autism, epilepsy, hyperactivity, foetal alcohol syndrome and schizophrenia. The high prevalence of Minor Physical Anomalies in schizophrenia provides considerable support for a neurodevelopmental model in this disorder. However, studies in large sample using standardised scale are lacking. Such studies are needed in order to confirm their actual frequency and study the clinical correlates or morphological anomalies. OBJECTIVE: The aim of this study was to revise and validate a French version of a scale designed for the evaluation of Minor Physical Anomalies in adult psychiatric patients and notably in patients with schizophrenia. METHODOLOGY: The scale was revised from the Waldrop scale. The choice of items was done on the basis of frequency, reliability in the adult, reliability of rating. Some new items, related to know syndroms with comportmental symptoms were added. Both raters had previously had a short initiation to the rating of the scale. Interrater reliability between two examiners, blind with regards to the diagnosis was evaluated. RESULTS: The interrater reliability was good, with an intraclass correlation coefficient at 0.97. Patients had significantly more minor physical anomalies than comparison subjects, and also more Minor Physical Anomalies than their parents. Fathers and mothers of these schizophrenic patients had significantly more Minor Physical Anomalies than normal comparison subjects. CONCLUSION: Although the evaluation of physical anomalies relies on subjective appreciation of normal vs abnormal, the revised version of minor physical anomalies scale (French version) was found to be a reliable tool, provided that a short initiation to the rating is performed. The scale differentiated schizophrenic patients from their parents, and the latter from the normal controls. A lot of questions remains unanswered concerning the neurodevelopmental hypothesis of schizophrenia. This scale appeared as a useful complementary tool to help in the determination of the developmental phenotypic status of the patients enrolled in pathophysiological studies aiming the identification of developmental factors in schizophrenia.     

Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder

This study examined the relation between childhood ocular alignment deficits and adult psychiatric outcomes among children at high-risk for schizophrenia and controls. A sample of 265 Danish children was administered a standardized eye exam assessing strabismus and related ocular alignment deficits. All children whose mothers or fathers had a psychiatric diagnosis of schizophrenia comprised the first group (N=90). Children who had at least one parent with a diagnosis other than schizophrenia comprised the first matched control group (N=93). The second control group consisted of children with no parental diagnoses (N=82). In 1992, adult psychiatric outcome data were obtained for 242 of the original subjects. It was found that children who later developed a schizophrenia-spectrum disorder had significantly higher eye exam scale and strabismus scale scores compared to children who developed other non-psychotic psychopathology and children who did not develop a mental illness. The mean rank for children in the high-risk group (offspring of parents with schizophrenia) on the eye scale and the strabismus scale was greater than the mean rank for children in the matched control groups (both offspring of parents with other non-psychotic disorder and no mental illness), although the results failed to reach statistical significance. Results from this study suggest a premorbid relation between ocular deficits and schizophrenia-spectrum disorders in childhood prior to onset of psychopathology in adulthood. Strabismus may serve as a premorbid marker for spectrum disorders and may have implications for the understanding of early aberrant neurological development related to later schizophrenia-spectrum disorders.     

Minor physical anomalies in childhood and adolescent onset schizophrenia

A modified version of the Waldrop scale (WS) was used to assess the prevalence of minor physical anomalies in schizophrenic patients (n = 71) and healthy controls (n = 65). The mean total WS score was 3.32 (SD 1.98) for the schizophrenic patients, significantly higher than that for the controls (2.19, SD 1.18). Minor physical anomalies were compared between two schizophrenic groups, divided on the basis of age at onset, early onset schizophrenia (EOS, onset under age 18 years) group and late onset schizophrenia (LOS, onset at or above age 20 years) group. The mean total WS score was 3.92 (SD 1.86) in the EOS group, significantly higher than the 2.59 (SD 1.79) in the LOS group. Minor physical anomalies are an indirect index for early prenatal central nervous system (CNS) maldevelopment; the present study indicated association between minor physical anomalies and EOS, thus a relationship between early prenatal CNS maldevelopment and EOS. These results support the hypothesis that EOS constitutes a subset of schizophrenia in which neurodevelopmental damage is largely involved.     

Discriminating value of total minor physical anomaly score on the Waldrop physical anomaly scale between schizophrenia patients and normal control subjects

Minor physical anomalies (MPAs) are slight structural aberrations that are believed to be associated with abnormal neurodevelopment. Studies of schizophrenia patients show that these patients score higher in MPAs than normal controls. The present study attempted to assess the potential value of MPAs as a classifying test in the status schizophrenia patient versus normal control. Seventy-six schizophrenia patients and 82 normal controls were assessed for MPAs using the Waldrop Physical Anomaly Scale, and specificity, sensitivity, and predictive value of the total MPA score were determined. A significantly higher percentage of schizophrenia patients than normal controls had high numbers of MPAs. Total MPA scores higher than 4 showed the most balanced set of sensitivity (76.3%), specificity (72.0%), and positive (71.6%) and negative (76.6%) predictive values for schizophrenia and were the cutoff scores that optimally discriminate schizophrenia patients from normal controls. Schizophrenia patients showed a higher percentage of subjects with prominent MPA scores. The results are consistent with the hypothesis that MPAs might reflect extragenetic stressful events and present total MPA score as a reliable index in distinguishing between schizophrenia patients and normal controls.     

Internal consistency of Waldrop Physical Anomaly Scale in schizophrenic patients

The aim of the study is to investigate the reliability (internal consistency) of the Waldrop Physical Anomaly Scale in patients with schizophrenia. The subjects were 76 schizophrenic patients (43 men, 33 women) and 82 normal controls (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. The correlations between the anomalies are low in schizophrenia, which indicates poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development. Some sex-related differences in the scale's reliability are indicated. The findings suggest the necessity of a more comprehensive scale by including informative morphogenetic variants, which can provide reliable anomaly assessment, distinguishing between minor malformations and phenogenetic variants and indicating the possible period of prenatal adversity.     

Impact of emotionality on memory and meta-memory in schizophrenia using video sequences

BACKGROUND AND OBJECTIVES: A vast amount of memory and meta-memory research in schizophrenia shows that these patients perform worse on memory accuracy and hold false information with strong conviction compared to healthy controls. So far, studies investigating these effects mainly used traditional static stimulus material like word lists or pictures. The question remains whether these memory and meta-memory effects are also present in (1) more near-life dynamic situations (i.e., using standardized videos) and (2) whether emotionality has an influence on memory and meta-memory deficits (i.e., response confidence) in schizophrenia compared to healthy controls. METHOD: Twenty-seven schizophrenia patients and 24 healthy controls were administered a newly developed emotional video paradigm with five videos differing in emotionality (positive, two negative, neutral, and delusional related). After each video, a recognition task required participants to make old-new discriminations along with confidence ratings, investigating memory accuracy and meta-memory deficits in more dynamic settings. RESULTS: For all but the positively valenced video, patients recognized fewer correct items compared to healthy controls, and did not differ with regard to the number of false memories for related items. In line with prior findings, schizophrenia patients showed more high-confident responses for misses and false memories for related items but displayed underconfidence for hits when compared to healthy controls, independent of emotionality. LIMITATIONS: Limited sample size and control group; combined valence and arousal indicator for emotionality; general psychopathology indicator. CONCLUSIONS: Emotionality differentially moderated memory accuracy, biases in schizophrenia patients compared to controls. Moreover, the meta-memory deficits identified in static paradigms also manifest in more dynamic settings near-life settings and seem to be independent of emotionality.     

Familial, obstetric, and other clinical correlates of minor physical anomalies in schizophrenia

OBJECTIVE: This study investigated possible antecedents of minor physical anomalies in schizophrenia, particularly in terms of obstetric and genetic factors, and demographic, clinical and cognitive correlates of such anomalies in schizophrenia. METHOD: Forty-one outpatients satisfying the DSM-III criteria for schizophrenia were examined for minor physical anomalies by using the Waldrop scale. These subjects were drawn from a group of 45 such patients whose cognitive function had been previously evaluated with Trail Making Tests A and B and whose biological mothers had been interviewed for any history of obstetric complications or family history of schizophrenia. RESULTS: Linear multiple regression analysis showed that higher scores for minor physical anomalies were associated with impaired cognitive flexibility on Trail Making Test B, family history of schizophrenia in a first-degree relative, maternal history of obstetric complications, smaller number of siblings, later position in the birth order, and male sex. A family history of schizophrenia was particularly associated with abnormalities of the mouth. The association between minor physical anomalies in the patients and obstetric complications in their mothers appeared to be confined to instances in which the mother had a history of bleeding in early pregnancy. CONCLUSIONS: Minor physical anomalies indicate early dysmorphogenesis in schizophrenia, particularly in males, which appears to be associated more reliably with genetic rather than obstetric factors and with cognitive impairment.     

Affective flattening and the criteria for schizophrenia.

The author used a scale that emphasizes objective behavioral signs to evaluate affective flattening and to rate affect in 69 patients suffering from schizophrenia (N = 30), mania (N = 19), and depression (N = 20). Raters were blind to the patient's diagnosis. Interrater reliability was assessed and found to be adequate to good for most items on the scale and for a global rating. The affective flattening was found to be common, but not omnipresent, in schizophrenia; it was also common among the depressed patients. The author recommends that affective flattening be considered as an important criterion for schizophrenia and that future research explore its frequency and prognostic significance.     

Increased prevalence of Chlamydophila DNA in post-mortem brain frontal cortex from patients with schizophrenia

Infection can initiate symptoms of mental illness. It has been shown previously that Chlamydophila DNA is present six times more often in the blood of patients with schizophrenia than in the blood of control individuals. Monocytes, the main targets of Chlamydiaceae infection, are microglia precursors. We identified Chlamydiaceae infection using blinded brain DNA samples derived from the frontal cortex. Using PCR and sequence analysis, we found Chlamydophila DNA to be four times greater in patients with schizophrenia than in controls (schizophrenia: N=34, microbial DNA frequency 23.5%; controls: N=35, microbial DNA frequency 5.7%; P=0.045, OR=5.08). Persistent Chlamydophila-infected microglia or neuronal cells may impair neuronal circuits and thus be a mechanism for causing psychiatric illness in these patients.     

5-羟色胺1A受体基因C（-1019）G多态性与精神分裂症的关联分析

目的:探讨云南地区汉族人群中5-羟色胺1A(5-HT1A)受体基因C(-1019)G多态性与精神分裂症的关联,及其对症状组成、前额叶执行功能的可能影响. 方法:应用阳性与阴性症状量表(PANSS)、简明精神病评定量表(BPRS)、外显攻击量表(OAS)等评定患者症状,威斯康星卡片分类测验(WCST)评定精神分裂症和正常人前额叶执行功能.142例精神分裂症患者和84名正常对照分别用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法进行基因分型. 结果:云南地区汉族人群中,5-HT1A受体基因启动子区C(-1019)G多态性在精神分裂症和正常人之间的各量表分差异有显著性(P=0.001).C(-1019)G多态性对PANSS中因子被动淡漠性社会退缩(N4)(P=0.010)、言语缺乏主动性和流畅性(N6)(P=0.004)、阴性症状总分(NT)(P=0.013)、紧张(G4)(P=0.005)、自发社交回避(G16)(P=0.013),以及BPRS中的因子4激活性(P=0.026)等条目得分的形成影响有显著性.C(-1019)G多态性与WCST各条目不相关. 结论:云南地区汉族人群中,5-HT1A受体基因启动子区C(-1019)G多态性与精神分裂症显著相关,对精神分裂症症状组成可能起一定作用,但与WCST反映的前额叶执行功能状态并无显著相关.     

晚发性和早发性精神分裂症临床特征比较

目的：了解早发性和晚发性精神分裂症的临床特征。方法：用阳性症状量表（SAPS）、阴性症状量表（SANS）评定临床症状;临床疗效总评量表（CGI）、治疗中出现的症状量表（TESS）评定临床疗效及不良反应;用躯体异常量表（Waldrop scale）N量软体征。对早发性精神分裂症和晚发性精神分裂症患者各50例进行对照研究。结果：早发性精神分裂症遗传倾向明显,软体征异常率高,有更明显的阴性症状,治疗效果较差,不良反应更明显。晚发性精神分裂症女性明显多于男性,以幻觉、妄想、偏执观念为主要临床特征．结论：早发性和晚发性精神分裂症各有其临床特征。早发性比晚发性精神分裂症的遗传负荷和胚胎发育异常程度高,治疗效果和预后较差。     

Sexual dimorphism in minor physical anomalies in schizophrenic patients and normal controls

The aim of the current study was to investigate the gender effecton minor physical anomalies (MPA) in schizophrenic patients and normal controls. Seventy-six schizophrenic patients (43 males and 33 females) and 82 normal control subjects (42 males and 40 females) were examined for MPA using a modified version of the Waldrop Physical Anomaly Scale. Men tended to be more stigmatized with MPA than women both in normal subjects and in schizophrenics (with this difference slightly expanding in schizophrenics). In both genders schizophrenic patients were significantly more likely to have MPA than normal controls, but the difference tended to be more pronounced in males. There was a tendency towards sex-related predilection for the increase of MPA in schizophrenics in terms of individual anomalies and topographic regions affected. Among schizophrenics, genders showed a somewhat opposite topography of MPA stigmatization, with relatively more pronounced peripheral dysmorphy in males and craniofacial dysmorphy in females. These data suggest greater vulnerability of the male fetus to endogenous or exogenous factors and different susceptibilities to developmental adversities in male and female schizophrenics. This finding is in accord with the increasing evidence that sex differences in the epidemiology of schizophrenia may be broader and more fundamental than previously thought.     

No association found between 158 Val/Met polymorphism of the COMT gene and schizophrenia with minor physical anomalies

The catechol-O-methyl transferase (COMT) gene has been a promising candidate in genetic research on schizophrenia because of its function in dopamine metabolism and its location on chromosome 22q11.2, which may be implicated in both schizophrenia and velocardiofacial syndrome (VCFS). To explore the possible genetic contribution of COMT to the development of schizophrenia, we focused on the subgroup of patients with schizophrenia characterized by minor physical anomalies as a phenotype and the 158 Val/Met polymorphism as a genotype. Since some physical anomalies are found in both schizophrenia and VCFS, schizophrenia patients with minor physical anomalies could represent the putative subgroup of schizophrenia linked to a disruption in neurodevelopment. Genotyping for the 158 Val/Met (472 G>A) polymorphism in the COMT gene was done for 239 patients with schizophrenia and 248 normal controls. Our analysis did not yield any significant between-group differences in terms of either allele or genotype frequency. We also could not find any association between the COMT gene and the schizophrenia subgroup with minor physical anomalies, although there was a significant difference in Waldrop total scores between the patients with schizophrenia and the normal controls. Analyses of subgroups based on other clinical variables also did not reveal significant differences. Overall, this study does not support the hypothesis that the 158 Val/Met polymorphism in the COMT gene is associated with schizophrenia in Koreans.     

Associations of anhedonia and cognition in persons with schizophrenia spectrum disorders, their siblings, and controls

The aim of the current study was to investigate the levels of social and physical anhedonia, as measured with the Chapman Scales for social and physical anhedonia in groups of patients with schizophrenia spectrum psychosis (n = 91), their unaffected siblings (n = 105), and control subjects drawn from a general population (n = 67). The second aim was to explore the effect of physical and social anhedonia on neuropsychological variables. Subjects with schizophrenia spectrum disorder had significantly more anhedonia than population controls, but the unaffected siblings did not differ from controls. Subjects with schizophrenia spectrum disorders had generalized cognitive deficits. Unaffected sibling status predicted impairments in executive and performance speed measures. Elevated physical anhedonia associated with deficits in verbal functions, but this was not related to genetic liability to schizophrenia. In conclusion, social and physical anhedonia did not seem to mediate neuropsychological deficits of schizophrenia family members.     

Personality traits in schizophrenia: comparison with a community sample

The objective of this study was to compare personality trait profiles in patients with schizophrenia and healthy controls. Male outpatients with schizophrenia (N = 24) and a male nonpsychiatric community sample (N = 46) completed the NEO-FFI personality questionnaire. Multivariate analyses were used to compare mean scale scores and scale profiles for each group. The overall personality profile of clinically stable patients with schizophrenia differed significantly from that of a community sample. On individual scales, patients scored significantly higher on neuroticism and significantly lower on conscientiousness. These results confirm and extend those of previous studies that used normative data for comparison and a much longer version of the same personality questionnaire. Prospective studies of populations at risk are needed to determine whether group differences reflect a premorbid diathesis for schizophrenia or a secondary effect of serious mental illness.     

Clinical signs of cerebellar dysfunction in schizophrenia,alcoholism, and their comorbidity

Abnormalities of cerebellar structure and function, long recognized as a hallmark of chronic alcohol abuse, have also occasionally been noted in patients with schizophrenia. We used a four-point rating scale to assess clinical signs of cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34) and alcohol dependence (N=15) as well as normal control subjects (N=28). Compared to controls, alcoholics had impaired ratings of gait ataxia and instability of stance with eyes closed, and schizophrenics had impaired ratings of stance with eyes closed. The incidence of dysdiadochokinesia was greater in schizophrenics, but not alcoholics, than controls. The incidence of gait and stance abnormalities was higher in both patient groups relative to controls: within the schizophrenic group, 50-70% of those with positive signs for gait or stance impairment were comorbid for alcoholism, while only 25% of those with positive signs for dysdiadochokinesia were comorbid for alcoholism. The presence of dysdiadochokinesia in the schizophrenic group suggests cerebellar dysfunction that is independent of the effects of alcohol. By contrast, clinical signs of cerebellar dysfunction of gait and stance in patients with schizophrenia may be secondary to the effects of alcohol on the cerebellum.     

Expanding the schizophrenia phenotype: a composite evaluation of neurodevelopmental markers

Minor physical anomalies (MPAs) and neurologic soft signs (NSSs) have been consistently reported to be more frequent in schizophrenia subjects and their first-degree relatives. We aimed at coassessing both these neurodevelopmental markers in neuroleptic-naive recent-onset schizophrenia (NRS) subjects in comparison to healthy control (HC) subjects to explore the predictive validity of this composite endophenotype. We administered the Modified Waldrop Scale (MWS) and the Neurological Evaluation Scale (NES) to evaluate MPAs and NSSs, respectively, in 40 NRS and 30 matched HC subjects. Schizophrenia subjects had significantly higher frequencies of MPAs and NSSs than HC. Minor physical anomaly total scores were correlated with greater severity of illness, whereas NES scores did not show any relationship with clinical variables. Schizophrenia and HC subjects were most accurately classified (82.9%) when MPAs and NSSs were considered as a composite phenotype rather than independently. Minor physical anomalies and NSSs constitute independent neurodevelopmental markers of schizophrenia and would afford greater predictive validity when used as a composite endophenotype in genetic association studies.     

Minor physical anomalies and schizophrenia spectrum disorders: a prospective investigation

OBJECTIVE: The authors prospectively assessed the relationship between minor physical anomalies identified in childhood and adult psychiatric outcome. METHOD: In 1972, minor physical anomalies were measured in a group of 265 Danish children ages 11-13. The examination was part of a larger study investigating early signs of schizophrenia spectrum disorders. Many of the subjects had a parent with schizophrenia, leaving them at high risk for developing a schizophrenia spectrum disorder. In 1991, adult psychiatric outcome data were obtained for 91.3% (N=242) of the original subjects, including 81 who were at high risk. RESULTS: Individuals with a high number of minor physical anomalies developed schizophrenia spectrum disorders significantly more often than they developed a no mental illness outcome. Further, individuals with a high number of minor physical anomalies tended to develop schizophrenia spectrum disorders more often than other psychopathology. Among individuals at genetic high risk, higher numbers of minor physical anomalies may interact with pre-existing vulnerabilities for schizophrenia to increase the likelihood of a schizophrenia spectrum disorder outcome. CONCLUSIONS: Minor physical anomalies may provide important clues to understanding schizophrenia spectrum disorders from a neurodevelopmental perspective. Minor physical anomalies appear to signal stressors relevant to schizophrenia spectrum development, especially in those at genetic risk for schizophrenia.     

Comparison of clinical characteristics and comorbidity in schizophrenia patients with and without obsessive-compulsive disorder: schizophrenic and OC symptoms in schizophrenia

BACKGROUND: Since a substantial proportion of schizophrenia patients has symptoms of obsessive-compulsive disorder (OCD), we sought to provide a phenomenological characterization of a schizophrenia subgroup with OCD. METHOD: A consecutive sample of patients who met DSM-IV criteria for both schizophrenia and OCD (N = 55) was compared with 55 schizophrenia patients without OCD matched for age and number of hospitalizations. Structured Clinical Interview for DSM-IV Axis I psychiatric disorders (SCID-I), including a specific module for tic disorders based on DSM-IV criteria, Scales for the Assessment of Positive and Negative Symptoms, Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impressions scale, and Hamilton Rating Scale for Depression were used. RESULTS: Schizophrenia patients with OCD (N = 55) had lower positive dimension scores than schizophrenia patients without OCD (N = 55) (p =.01). Two subgroups of schizo-obsessive patients were identified: OCD independent of schizophrenia symptoms and OCD partially overlapping positive schizophrenia symptoms. Schizophrenia patients with OCD had more SCID-detectable OCD-spectrum disorder, primarily body dysmorphic disorder and chronic tic disorders. More schizophrenia patients with OCD were treated with either add-on serotonin reuptake inhibitors or clozapine. CONCLUSION: Schizophrenia patients with OCD differ from their non-OCD-schizophrenia counterparts in severity of schizophrenia symptoms, co-occurrence of OCD-spectrum disorders, and pharmacotherapy. These findings and the identification of 2 subgroups of schizo-obsessive patients support the validity of this unique clinical entity and may facilitate the establishment of diagnostic criteria for a schizo-obsessive subtype of schizophrenia.